Stressful signals are transduced through various signalling pathways, ultimately resulting in alteted gene expression, including that of cycle regulatory genes. While the transcriptional events regulating the expression of stress- response genes have been thoroughly studied, it is becoming increasingly clear that post-transcriptional regulatory mechanisms also play a critical role in their induction by stress. These post-transcriptional processes, still poorly understood, include mRNA splicing, transport, subcellular localization, stability and translation, as well as post- translational events such as protein processing, transport, phosphorylation and degradation. With respect to mRNA stability, we are studying the expression of the inhibitor of cyclin-dependent kinases p21, which is induced by various stresses (such as ultraviolet light C) through stabilization of its mRNA. Much effort is focused on searching for RNA regions and proteins involved in regulating the stability of p21 and other stress-reponse genes, particularly those involved in growth control and cell cycle regulation. This analysis involves both in vitro and in vivo determinations of RNA binding and RNA degradation, the identification of the RNA-binding proteins involved and the signalling pathways that modulate their activity. We are also studying the function of the tumor suppressor gene von Hippel-Lindau (VHL). The VHL protein is believed to function in modulating gene expression at the levels of transcription elongation, mRNA stability and protein degradation. We are examining the function of the VHL tumor suppressor gene within the stress response.